Inflammatory bowel disease.
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Azathioprine↗
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Review article: bone disease in inflammatory bowel disease.
Inflammatory bowel disease (IBD) is associated with an increased incidence of osteoporosis. Osteoporosis with osteoporotic pain syndromes, fragility fractures and osteonecrosis accounts for significant morbidity and impacts negatively on the quality of life. It is generally agreed that there is a need to increase awareness for inflammatory bowel disease-associated osteoporosis. However, the best ways in which to identify at-risk patients, the epidemiology of fractures and an evidence-based rational prevention strategy remain to be established. The overall prevalence of IBD-associated osteoporosis is 15%, with higher rates seen in older and underweight subjects. The incidence of fractures is about 1 per 100 patient years, with fracture rates dramatically increasing with age. While old age is a significant risk factor, disease type (Crohn's disease or ulcerative colitis) is not related to osteoporosis risk. Corticosteroid use is a major variable influencing IBD-associated bone loss; however, it is difficult to separate the effects of corticosteroids from those of disease activity. The recommendations in inflammatory bowel disease are similar to those for postmenopausal osteoporosis, with emphasis on lifestyle modification, vitamin D (400-800 IE daily) and calcium (1000-1500 mg daily) supplementation and hormone replacement therapy (oestrogens/selective oestrogen receptor modulators in women, testosterone in hypogonadal men). Bisphosphonates have been approved for patients with osteoporosis (T-score < 2.5), osteoporotic fragility fractures and patients receiving continuous steroid medication. Data on the recently Food and Drug Administration-approved osteoanabolic substance parathyroid hormone and on osteoprotegerin are promising in terms of both steroid-induced and inflammation-mediated osteoporosis, the key elements of inflammatory bowel disease-associated bone disease.
Adrenal Cortex Hormones↗
The role of indium-111 white blood cells in inflammatory bowel disease.
Inflammatory bowel disease in patients may be difficult to diagnose because of the complex problems associated with this disease. Radionuclides are able to provide a rapid and effective method of imaging the bowel in patients with active inflammatory bowel disease. In the past, clinical work-ups have included barium x-ray studies and endoscopy. Scarring and fistula formation have made it difficult to determine between the active disease and abscesses that may occur. Gallium-67 (67Ga) has been very useful in imaging patients with inflammatory bowel disease, but the multiple-day imaging procedure has been a limitation for the clinicians when achieving a diagnosis. Recent results with Indium-111 (111In)--labeled WBCs have provided excellent correlation between clinical symptoms and colonoscopy findings in patients with inflammatory bowel disease. This technique has also allowed the differentiation between reoccurring inflammatory bowel disease and abscesses that accompany the disease within a 24-hour time period. The use of intravenous (IV) glucagon has increased the clarity of the images in the small bowel. Technetium 99m (99mTc) diethylenetriaminepentaacetic acid (DTPA) has been used in patients with inflammatory bowel disease demonstrating promising results. Investigators feel labelling 99mTc with WBCs will be improved, therefore yielding a greater efficiency, which will have a major impact on imaging patients with inflammatory bowel disease. Imaging patients with inflammatory bowel disease using radionuclides has yielded promising results. This is a significant advancement over barium radiography and endoscopy exams.
Humans↗
Leukocytapheresis as an adjunct to conventional medication for inflammatory bowel disease.
Inflammatory bowel disease is characterized by clinical remission and relapse caused by severe intestinal inflammation. Drug therapy for inflammatory bowel disease is associated with unpleasant side effects. Furthermore, efficacy of conventional drugs decreases with chronic use, which can be a major difficulty in the long-term management of this disease. In active inflammatory bowel disease, leukocytes are elevated with activation behavior and increased survival time, and mucosal neutrophil level parallels the severity of intestinal inflammation and predicts relapse. Leukocyte-derived inflammatory cytokines are suspected to be major factors in the initiation and perpetuation of inflammatory bowel disease. Accordingly, leukocytes should be appropriate targets for therapy. To reduce peripheral blood level of leukocytes, centrifugation has been used to deplete peripheral blood leukocytes; this provided the initial evidence that reducing the level of peripheral blood leukocytes can benefit patients with inflammatory disease. To overcome the limitations of centrifugation, membrane filters, such as the Cellsorba trade mark column and leukocyte-adsorbing beads containing column like Adacolumn, have been developed that are direct blood perfusion systems for removing any desired level of leukocytes. In initial independent clinical studies, these two new models have produced striking clinical efficacy, safety, and a marked reduction in the dose of corticosteroids used to induce remission of active inflammatory bowel disease. Leukocytapheresis has been associated with a significant decrease in the amount of several proinflammatory cytokines produced by peripheral blood leukocytes. Accordingly, the Japan Ministry of Health has now approved both methods for the treatment of active ulcerative colitis. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy for inflammatory bowel disease to promote remission, taper conventional drug dosage, and potentially reduce the number of patients who require colectomy. The results should further understanding of the pathophysiology of inflammatory bowel disease.
Anti-Inflammatory Agents↗
Pediatric inflammatory bowel disease.
Inflammatory bowel disease is an important cause of gastrointestinal pathology in children and adolescents. The incidence of pediatric inflammatory bowel disease is increasing; therefore, it is important for the clinician to be aware of the presentation of this disease in the pediatric population. Laboratory tests, radiology studies, and endoscopic procedures are helpful in diagnosing inflammatory bowel disease and differentiating between Crohn's disease and ulcerative colitis. Once diagnosed, the goal of medical management is to induce remission of disease while minimizing the side effects of the medication. Specific attention needs to be paid to achieving normal growth in this susceptible population. Surgical management is usually indicated for failure of medical management, complication, or malignancy. Algorithms for diagnostic evaluation and treatment of pediatric inflammatory bowel disease are presented. The specific psychosocial issues facing these patients are also discussed in this review as are the future goals of research in the complex problem of pediatric inflammatory bowel disease.
Adolescent↗
[Osteoporosis associated with inflammatory bowel diseases].
Inflammatory bowel diseases, most frequently Crohn's disease, are frequently accompanied by decreased bone mineral content (30-70%). The osteopenia is not explained by the side effects of treatment or the secondary malabsorption. There must be a common pathological pathway in the background. The mineral content of bones is most easily measured by dual-ray absorptiometry. The measurement should be performed at the time of the diagnosis of bowel disease. It is useful to perform some routine laboratory examinations (serum calcium and phosphate, urinary calcium excretion level, etc.) and some special tests (serum osteocalcin and crosslaps) to exclude some other pathological pathways as well as to plan the anti-osteoporotic therapy. Appropriate calcium and vitamin-D supplementation is essential in prevention and therapy as well. Several drug-classes have proven useful in the therapy of severe osteoporosis associated with inflammatory bowel diseases such as bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators and calcitonin. The authors provide an algorithm for the therapy of metabolic bone disease in inflammatory bowel disease.
Absorptiometry, Photon↗
Pharmacological nutrition in inflammatory bowel diseases.
Inflammatory Bowel Diseases--ulcerative colitis and Crohn's disease--are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted. Total parenteral nutrition has been used to correct and prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with a high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission of disease in adults and promoting growth in children. Recent research has focused on the use of specific nutrients as primary treatment agents. Although some reports have indicated that glutamine, short-chain fatty acids, antioxidants and immunonutrition with omega-3 fatty acids are an important therapeutic alternative in the management of inflammatory bowel diseases, the beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these nutrients still need further evaluation through prospective and randomized trials.
Colitis, Ulcerative↗
[Genotype-phenotype associations in inflammatory bowel disease].
Inflammatory bowel disease has traditionally been categorized as either ulcerative colitis or Crohn's disease on the basis of clinical, radiological and histological criteria. Emerging data suggest that inflammatory bowel disease comprises a heterogenous family of inflammatory disorders in which the specific clinical manifestations of disease are determined by the interaction of genetic and environmental factors. Interactions of susceptibility and modifying genes influence the specific features of disease phenotype, penetrance, location, behavior, and complication. CARD15/NOD2 mutations are significantly associated with ileal location, whereas certain HLA haplotypes are associated with colonic disease. The associations with CARD15/ND2 mutations and early age at onset, as well as disease behavior (stricturing, fistulizing type) are less consistent. Distinct HLA alleles contribute to the occurrence of extraintestinal manifestation. With the increasing number of genotype-phenotype relationship, it is hoped that a molecular classification can be created, in which various disease subtypes are categorized according to their specific genotypes. In the future, such sheme may permit early, accurate diagnosis, prediction of disease course, complications, prognosis, as well as treatment response.
Age of Onset↗
Clinical economics review: medical management of inflammatory bowel disease.
Inflammatory bowel diseases, although they are uncommon and rarely fatal, typically present during the period of economically productive adult life. Patients may require extensive therapeutic intervention as a result of the chronic, relapsing nature of the diseases. Their medical management includes oral and topical 5-amino salicylic acid derivatives and corticosteroids, as well as antibiotics and immunosuppressive therapies. Assessing the cost-effectiveness of rival treatments requires valid, reliable global assessments of outcome which consider quality of life, as well as the usual clinical end-points. Macro-economic studies of the overall impact of inflammatory bowel disease on health care systems have so far been largely confined to North America, where the total annual US costs, both direct and indirect, incurred by the estimated 380 000-480 000 sufferers has been put at around US2bn. Drugs were estimated to account for only 10% of total costs, whereas surgery and hospitalization account for approximately half. Studies from Europe suggest that the proportion of patients with Crohn's disease and ulcerative colitis who are capable of full time work is 75% and 90%, respectively. However, whilst only a minority of inflammatory bowel disease patients suffer chronic ill health and their life expectancy is normal, obtaining life assurance may be problematic, suggesting a misconception that inflammatory bowel disease frequently results in a major impact on an individual's economic productivity.
Colitis, Ulcerative↗
Neutropenia is not required for clinical remission during azathioprine therapy in inflammatory bowel disease.
Inflammatory bowel disease is an idiopathic chronic inflammatory process of the gastrointestinal tract. The aetiology remains unknown but probably involves a combination of genetic susceptibility, environmental triggers and abnormal immune regulation. Immunomodulators are effective in treating inflammatory bowel disease. Azathioprine and 6-mercaptopurine (6MP) are the most frequently used immunomodulator agents. These agents are probably underused by many clinicians because of concerns about myelosuppression, pancreatitis, allergic reactions and hepatotoxicity, which can occur in a fraction of patients taking these drugs. Therefore, clinicians have sought ways to optimize therapeutic response and limit toxic side effects. Neutropenia, although uncommon, can occur in patients taking azathioprine or 6MP. The question of neutropenia effecting clinical response has been raised as a possible indicator of therapeutic response. In the study from Campbell and Ghosh [7] in this issue of the European Journal of Gastroenterology and Hepatology, no difference in relapse rates was noted between neutropenic and non-neutropenic patients. In fact, severe life-threatening neutropenia was seen in four patients.
Azathioprine↗
Prospects for research in inflammatory bowel disease.
Inflammatory bowel disease is a chronic inflammatory condition of the gastrointestinal tract that manifests as ulcerative colitis and Crohn disease. Both these clinical entities result from interrelated genetic and environmental factors that may be channeled through an abnormality in mucosal immune function, possibly due to dysregulated or excessive T helper cell (T(H))1 (Crohn disease) or T(H)2 (ulcerative colitis) responses. This article reviews current knowledge of the role of immune factors in inflammatory bowel disease and the potential therapeutic strategies that target the pathways of T(H)1- or T(H)2-induced inflammation.
Animals↗
Interleukin-1 in the pathogenesis of and protection from inflammatory bowel disease.
Inflammatory bowel disease affects millions of people, some with fatal consequences. Little is known about the factors which contribute to its pathogenesis particularly regarding cytokine production and action. In this paper we summarize our recent findings using the rabbit model for immune complex-generated experimental colitis, a model which is similar to ulcerative colitis in humans. Recombinant human IL-1 was perfused through rabbit colons and we observed elevated levels of PGE2, TxB2 and 6-keto-PGF1 alpha, the stable metabolite of PGI2. Using radioimmunoassays specific for rabbit IL-1 alpha and IL-1 beta, we induced immune complex colitis and measured the generation of these IL-1's in various tissues. Markedly elevated levels of IL-1 were detected only in inflamed tissues. The levels of IL-1 correlated with the degree of inflammation as judged by a blinded assessment of pathological changes. Similar to other disease models in which small doses of the agonist can afford protection or result in a state of "desensitization" when administered prior to the onset of the disease, we accordingly injected rabbits with a single, small (300 ng/kg) dose of IL-1 and observed a significant reduction in the inflammatory index and necrosis of immune complex colitis. However, unlike other models of IL-1-induced protection, in this model cyclooxygenase products were required since we prevented the IL-1-induced protection with a single dose of ibuprofen given at the same time as the IL-1. This correlated with the reduction in IL-1-induced PGE2. These results demonstrate that IL-1 plays a key role in the pathogenesis of inflammatory bowel disease in the rabbit and that the protection afforded by a low dose of IL-1 24 hours before the onset of the colitis requires IL-1-induced cyclooxygenase products.
Animals↗
[Immunopathogenesis of inflammatory bowel diseases].
Inflammatory bowel diseases (IBD: Crohn's disease, ulcerative colitis) are chronic inflammatory and frequently relapsing diseases of the gut that ultimately lead to destruction of the intestinal tissue. Recent evidence suggests that a pathologic activation of the mucosal immune system in response to antigens is a key factor in the pathogenesis of IBD. Furthermore, changes in cell migration and cytokine production appear to contribute to the perpetuation of IBD and the postoperative recurrence of Crohn's disease. Based on recent advances in our understanding of the pathogenesis of IBD, several new therapeutic strategies are currently being tested in clinical practice, including recombinant anti-inflammatory cytokines (IFN-alpha, IL-10, IL-11) and inhibitors of cell adhesion molecules (ICAM), proinflammatory cytokines (TNF, IL-12) and their receptors (TNF, IL-6R).
Adjuvants, Immunologic↗
Extraintestinal manifestations of inflammatory bowel diseases.
Inflammatory bowel diseases are associated with extraintestinal manifestations involving almost every organ system in the body. They occur in approximately 20% to 40% of patients with inflammatory bowel diseases. Immune-related and genetic mechanisms play an important role in the pathogenesis of these complications. Peripheral arthritis, erythema nodosum, and episcleritis respond to the treatment of the underlying intestinal inflammation, whereas axial arthropathy, pyoderma gangrenosum, and uveitis do not. Immunomodulator therapy, particularly with biologic agents has been shown to be effective in treating some of the extraintestinal manifestations. Early recognition and treatment are crucial in preventing major morbidity.
Autoimmunity↗
Probiotic lactobacilli: a new perspective for the treatment of inflammatory bowel disease.
Inflammatory bowel disease, such as ulcerative colitis and Crohn's disease, results from an interaction between susceptibility genes, the host's bacterial environment, gut barrier defects, and immunological factors. New management approaches have been evolved from advances in our understanding of the pathobiology of this common gut disorder In particular, the therapeutic manipulation of the bacterial microenvironment in the gut seems to offer an innovative tool for the treatment of those patients. Since the gut is a highly sensitizing organ that contributes to the systemic immune response, potent treatments need to be developed to reduce gut inflammation in this disorder. Recent studies have demonstrated that probiotic lactobacilli, and also immunostimulatory DNA sequences from those same bacteria have an important anti-inflammatory potential in this context. Future research should better define among patients with inflammatory bowel disease the various clinical phenotypes with the greatest potential of response to probiotic treatment. Identification of the genes leading to the disease and a rather better understanding of the underlying immunoregulatory abnormalities will be crucial steps to define the different profiles of interaction between endogenous digestive bacterial flora and the immune system in each individual patient. Such advances will probably lead to targeting of effective treatments, including bacteriotherapy with probiotic lactobacilli, to subsets of patients with inflammatory bowel disease.
Animals↗
The use of questionnaires in pediatric inflammatory bowel disease.
Inflammatory bowel disease is a chronic illness with symptoms including abdominal pain, weight loss, chronic diarrhea, hematochezia, and growth failure. It affects both children and adults. The goal of management is to induce and maintain clinical remission and to reduce psychosocial and quality of life issues caused by the disease. Various questionnaires have been developed to help physicians and investigators gain information regarding health-related quality of life, treatment satisfaction, disease activity, and disease-specific knowledge. The purpose of this review is to discuss the questionnaires available to clinicians treating children and adolescents with inflammatory bowel disease.
Child↗
New insights into the immunopathology of chronic inflammatory bowel disease.
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestine encompassing Crohn's disease (CD) and ulcerative colitis (UC). The inflammation in CD can extend anywhere along the alimentary canal, whereas in UC the inflammation is limited to the large bowel. In CD the inflammation is typically patchy, transmural, and contains noncaseating granulomata, whereas in UC the inflammation is relatively superficial with ulcer formations. Nonetheless, 10% of the cases are clinically and histologically identical. Both disorders are idiopathic, because no etiological agent can be found, and both show autoimmune characteristics. However, the underlying immunological mechanism is still very poorly understood and controversial. Therefore the treatment of IBD, has, thus far, been unsatisfying, because it involves the administration of rather unspecific immunosuppressive agents. To find more specific therapies, it is necessary to study the underlying immunopathological mechanism of the disease.
Animals↗
Inflammatory bowel disease.
Inflammatory bowel disease is a complicated condition, including Crohn's disease, ulcerative colitis, microscopic colitis, and indeterminate colitis, that affects the intestine and several extraintestinal sites. There has been much debate regarding whether Crohn's disease and ulcerative colitis are distinct entities or if they exist along a continuum of the same disease process. In this article, the pathogenic mechanisms and clinical manifestations of inflammatory bowel disease are reviewed, as well as treatment options. Because Crohn's disease and ulcerative colitis are chronic diseases, they have an important economic effect on our healthcare system and the United States as a whole. Some newer and more expensive treatment options may provide overall cost savings in select patient populations because of decreased use of healthcare resources.
Humans↗